Articular cartilage is a hydrated and lubricated joint tissue that allows for the relative movement of opposing joint surfaces under high loads (Buckwalter et al. (1998)). A sparse distribution of chondrocytes reside in the dense extracellular matrix of the tissue, with components such as collagen, proteoglycan and water inhomogenously dispersed through the depth of the tissue.
Mature articular cartilage does not possess an intrinsic ability to heal, since it is avascular and lacks a source of mesenchymal cells (Buckwalter et al. (1998)). Therefore, small focal cartilage defects can propagate unchecked to include the entire joint, eventually leading to osteoarthritis (OA) (Buckwalter et al. (1998)), a condition which affects as many as 27 million Americans with societal costs greater than $15 billion annually (Woolf et al. (2003): Gelber et al. (2000)). Current operative procedures for the treatment of articular cartilage damage generally fall into four categories: 1. nontransplant salvage operations such as abrasion arthroplasty; 2. mosaicplasty in which a cartilage-bone plug is transplanted into a joint which is minimally weight bearing; 3. reimplantation of autogenously isolated and expanded cells; and 4. the implantation of allografts (Maher et al. (2007); Szerb et al. (2005); Freedman et al. (2003); Brittburg et al. (2003); Gross (2003)). However, all of these techniques have their limitations, and do not prevent the progression of the osteoarthritis, which often propagates from the focal defect. Furthermore, over 33% of those affected by arthritis are under age 65. Accordingly, the number of young patients with total knee replacement, the end stage treatment for arthritis, is increasing. Performance of joint replacements in younger patient populations is less satisfactory than for older patients, oftentimes leading to multiple revision surgeries, each with successively diminishing longevity.
The problem with many of the surgical approaches and implantable materials that have been developed thus far, is the inability to integrate with the native tissue. For example, microfracture, the most commonly used clinical procedure for the treatment of full-thickness defects, results in poor integration between the fibrocartilage tissue that fills the defect site and the surrounding host tissue hyaline cartilage (Lane et al. (2010); Fortier et al. (2010); Gill et al. (2005); Hoemann et al. (2005); Watanabe et al. (2009); Hattori et al. (2008); LaPrade et al. (2008); Morisset et al. (2007); Kreuz et al. (2006)). Osteochondral autograft transfer is another technique developed to fill osteoarticular defects in weight bearing regions of the knee (Bobic (1996); Hangody et al. (1998)). However, chondrocyte death at the margins of the autograft (Evans et al. (2004); Zhang et al. (2005); Hunziker et al. (2003); Enders et al. (2010)) and persistent gaps between the graft and the host tissue (Kock et al. (2004); Lane et al. (2004); Williams et al. (2007); Marquass et al. (2010)) have been shown to lead to poor graft durability over time (Solheim et al. (2010)). In cases where implants are used to fill the defect, margin integration is frequently characterized by gaps and fissuring in histologic sections (Schafer et al. (2002); Niederauer et al. (2000); Wegener et al. (2010); Nehrer et al. (1998); Jiang et al. (2007); Ito et al. (2005); Wang et al. (2010)).
Efforts to create a mechanically stable interface between an implant and the host articular cartilage have explored the use of partial enzymatic digestion of the host tissue (Obradovic et al. (2001); Hunziker et al. (1998)) and the release of chemotactic agents to increase the number of matrix generating cells at the interface (Pabbruwe et al. (2009); Fortier et al. (2002)). Such approaches may help to reinforce the boundary between the scaffold and the host tissue as a function of time, but they do not address the problems associated with an initially unstable interface. Newer approaches rely on the use of an adhesive agent as an intermediary that chemically binds the native tissue to the implant in an attempt to immediately “glue” the scaffold to the surrounding native cartilage. One such example involves using a functionalized chondroitin sulphate paste to create a covalent bond between a biomaterial and proteins in articular cartilage (Wang et al. (2007); Strehin et al. (2010)). While the technology has been demonstrated to increase the interfacial strength and percent tissue fill in scaffold implanted cartilage defects, the addition of yet another interface (that between the glue and the implant and the implant and the cartilage) is far from ideal.
Therefore, there is a need in the art for a more reliable method to treat patients with focal defects, especially young active ones, early in the course of the problem, thus delaying or eliminating the need for total joint replacement, and a real need in the art for composition and method which increases focal strength and integration of an implant in a short period of time after implantation.